This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. HYPOTHESIS It is proposed that the ability of CD40 Ligand (CD40L) to enhance leukemia antigen presentation in vivo, to act as a co-stimulator molecule and to induce hIL-2 release all serve to recruit both specific T cell and NK cell anti-leukemia effector mechanisms, which hIL-2 is then able to further amplify. -To determine the safety of three to six subcutaneous (SC) injections of autologous malignant B cells from chronic lymphocytic leukemia (B-CLL) patients, which have been modified ex vivo to secrete human interleukin-2 (hIL-2) and to express human CD40 ligand (hCD40L). -To determine whether MHC-restricted or unrestricted anti-tumor immune responses are induced by SC injections of B-CLL cells which have been modified ex vivo to secrete hIL-2 and to express hCD40L. -To obtain preliminary data on the anti-timor effects of this treatment regimen.